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Distinct Glycoprotein Ib/V/IX and Integrin αIIbβ3-dependent Calcium Signals Cooperatively Regulate Platelet Adhesion under Flow
Open accessAbstract
We have investigated the calcium signaling relationship between the two major platelet adhesion receptors, glycoprotein Ib/V/IX (GPIb/V/IX) and integrin alpha(IIb)beta(3), involved in regulating platelet adhesion on von Willebrand factor (vWf) under flow. Our studies demonstrate that GPIb engagement of immobilized vWf elicits a transient calcium spike that may function to promote reversible arrest of translocating platelets. Subsequent integrin alpha(IIb)beta(3) engagement of vWf promotes sustained calcium oscillations that are essential for the maintenance of irreversible adhesion. GPIb-induced calcium spikes appear distinct from those initiated by integrin alpha(IIb)beta(3), in that the former are exclusively mediated through release of intracellular calcium stores via a signaling mechanism independent of PI 3-kinase. In contrast, integrin alpha(IIb)beta(3)-dependent calcium flux involves a PI 3-kinase-dependent signaling mechanism linked to intracellular calcium mobilization and subsequent transmembrane calcium influx. Studies employing the caged calcium chelator (o-nitrophenyl-EGTA) demonstrate that transient calcium spikes initiate a transient phase of platelet arrest that is converted to irreversible adhesion with the development of sustained oscillatory calcium flux. These studies demonstrate the existence of a dual step calcium signaling mechanism utilized by GPIb and integrin alpha(IIb)beta(3) that serves to regulate the dynamics of platelet adhesion under flow.
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Cites
Activation of Phospholipase C-γ by Phosphatidylinositol 3,4,5-Trisphosphate
Bae, Y. S., Cantley, L. G., Chen, C.-S., Kim, S.-R., Kwon, K.-S., & Rhee, S. G. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.8.4465 · Cited by 330
Cited by
PI 3-kinase p110β: a new target for antithrombotic therapy
Jackson, S. P., Schoenwaelder, S. M., Goncalves, I., Nesbitt, W. S., Yap, C. L., Wright, C. E., Kenche, V., Anderson, K. E., Dopheide, S. M., Yuan, Y., et al. (2005) · Nature Medicine · doi:10.1038/nm1232 · Cited by 580
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Metadata
- Authors
- Nesbitt, W. S., Kulkarni, S., Giuliano, S., Goncalves, I., Dopheide, S. M., Yap, C. L., Harper, I. S., Salem, H. H., & Jackson, S. P.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2002-01
- Volume
- 277
- Issue
- 4
- Pages
- 2965-2972
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1976738617
- Cited by
- 183
- References
- 1
- FWCI
- 6.50
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Nesbitt, W. S., Kulkarni, S., Giuliano, S., Goncalves, I., Dopheide, S. M., Yap, C. L., Harper, I. S., Salem, H. H., & Jackson, S. P. (2002). Distinct Glycoprotein Ib/V/IX and Integrin αIIbβ3-dependent Calcium Signals Cooperatively Regulate Platelet Adhesion under Flow. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m110070200
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
